Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
BMC Med Educ ; 24(1): 454, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664692

RESUMO

BACKGROUND: Transgender and gender diverse (TGD) individuals face barriers, including harassment and discrimination, when accessing healthcare services. Medical imaging procedures require personal information to be shared, such as date of last menstrual cycle and/or pregnancy status; some imaging exams are also invasive or intimate in nature. Terminology is based on binary sex creating an inherently cis-heteronormative environment. TGD patients fear being outed and often feel a need to function as educators and advocates for their care. Incorporation of inclusive healthcare curriculum related to TGD populations is an effective means of educating new health providers and promotes safer and more inclusive spaces in healthcare settings. Educators face barriers which hinder the creation and implementation of TGD content. The purpose of this study was to examine the impacts educators are faced with when creating and delivering TGD content in their medical imaging curriculum. METHODS: A case study of medical imaging programs at a Canadian post-secondary institute was undertaken. Data was collected via semi-structured interviews with faculty. Relevant institutional documents such as strategic plans, policies/procedures, websites, and competency profiles were accessed. Framework analysis was used to analyze the data. RESULTS: The study found seven themes that influence the development of TGD curriculum as follows: familiarity and comfort with the curriculum and content change process; collaboration with other healthcare programs; teaching expertise; management of course workload and related. duties; connections to the TGD community; knowledge of required TGD content and existing gaps in curriculum; and access to supports. CONCLUSIONS: Understanding educators' perspectives can lead to an increased sense of empowerment for them to create and incorporate TGD curriculum in the future. Many post- secondary institutions are incorporating an inclusive lens to educational plans; this research can be used in future curriculum design projects. The goal is improved medical imaging experiences for the TGD population.


Assuntos
Currículo , Pessoas Transgênero , Humanos , Feminino , Canadá , Masculino , Diagnóstico por Imagem
2.
Acta Oncol ; 62(1): 62-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36645166

RESUMO

INTRODUCTION: Treatment with immune checkpoint inhibitors (ICI) has expanded into the adjuvant setting enhancing the importance of knowledge on the immune-related toxicities and their impact on health-related quality of life (HRQoL). Large phase 3 trials of patients with resected Stage III/IV melanoma found no effect on HRQoL during adjuvant immunotherapy. This study investigates how HRQoL was affected during and after adjuvant immunotherapy in a real-world setting. METHODS: Patients with resected melanoma treated with adjuvant nivolumab from 2018 to 2021 in Denmark were identified using the Danish Metastatic Melanoma Database (DAMMED). The study was performed as a nationwide cross-sectional analysis as a questionnaire consisting of six different validated questionnaires on HRQoL, cognitive function, fatigue, depression, fear of recurrence, and decision regret was sent to all patients in March 2021. To evaluate HRQoL during and after adjuvant treatment, patients were divided into groups depending on their treatment status when answering the questionnaire; patients in active treatment for 0-6 months, patients in active treatment for >6 months, patients who ended treatment 0-6 months ago, and patients who ended treatment >6 months ago. RESULTS: A total of 271/412 (66%) patients completed the questionnaire. Patients who ended therapy 0-6 months ago had the lowest HRQoL and had more fatigue. Patients in active treatment for >6 months had lower HRQoL and more fatigue than patients who started treatment 0-6 months ago. Patients ending therapy >6 months ago had higher HRQoL and less fatigue compared to patients who ended therapy 0-6 months ago. Multivariable analysis showed an association between HRQoL and treatment status, comorbidity, civil status, and employment status. CONCLUSIONS: Adjuvant nivolumab may affect some aspects of QoL, but the influence seems temporary. Patient characteristics, such as civil status, employment status, and comorbidity were associated with HRQoL.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Nivolumabe , Qualidade de Vida , Saúde Mental , Estudos Transversais , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/patologia , Imunoterapia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Melanoma Maligno Cutâneo
3.
Acta Oncol ; 61(1): 45-51, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34666597

RESUMO

BACKGROUND: Combination therapy with BRAF and MEK inhibitors (BRAF/MEKi) has significantly improved the outcome for patients with BRAF-mutated melanoma. A reduction in left ventricular ejection fraction (LVEF) is a known side effect during treatment with BRAF/MEKi. This study aimed to analyze sequential multigated acquisition (MUGA) scans for the evaluation of LVEF and provide real-world data on cardiotoxicity induced by BRAF/MEKi in advanced melanoma. METHODS: All patients with advanced melanoma treated with dabrafenib and trametinib at Herlev and Gentofte Hospital, Denmark, between March 2015 and September 2019, were included retrospectively. MUGA scans performed at baseline and every three months during treatment were analyzed. Cardiotoxicity was defined as a decline of ≥10 percentage point (pp) to an LVEF <50% (major cardiotoxicity) or a decline in LVEF of ≥15 pp but remaining >50% (minor cardiotoxicity). RESULTS: A total of 139 patients were included. Forty-six patients (33%) met our criteria for cardiotoxicity; 31 patients (22%) experienced minor cardiotoxicity and 15 patients (11%) experienced major cardiotoxicity. Median time to decline in LVEF was 94 days, and all clinically significant declines in LVEF occurred before evaluation at six months. Reversibility of LVEF was seen in 80% of patients, three patients were not evaluable for reversibility. A low left ventricular peak emptying rate adjusted for heart rate (LVPERadj) at baseline was found a potential risk factor for the development of major cardiotoxicity (RR = 0.159, p = 0.001). CONCLUSION: A decline in LVEF is common for patients with advanced melanoma treated with BRAF/MEKi but rarely clinically significant. No significant decline in LVEF was observed after evaluation at six months, therefore routine monitoring of LVEF might be stopped after six to nine months of BRAF/MEKi therapy. A low LVPERadj might be a risk factor for the development of cardiotoxicity and is suggested for further investigation.


Assuntos
Melanoma , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica , Cardiotoxicidade/etiologia , Humanos , Melanoma/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Volume Sistólico , Função Ventricular Esquerda
4.
Br J Clin Pharmacol ; 87(4): 1963-1969, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33118168

RESUMO

AIMS: Recently a limited sampling strategy (LSS) for determination of metformin' pharmacokinetics was developed. The LSS utilizes the plasma concentration of metformin 3 and 10 hours after oral intake of a single dose to estimate the area under the concentration-time curve up to 24 hours (AUC0-24h ). The main purpose of this study was to support the feasibility of this strategy in a large prospective trial. METHODS: Volunteers orally ingested two 500-mg tablets of metformin hydrochloride. A blood sample was drawn three and ten hours after the ingestion. Urine was collected for 0-10 and 10-24 hours and urine volumes recorded. The AUC0-24h was calculated using the equation AUC0-24h = 4.779 * C3 + 13.174 * C10 . Additionally, all participants were genotyped for the single-nucleotide polymorphism A270S in OCT2, g.-66 T > C in MATE1, R61C, G465R, G401S and the deletion M420del in OCT1. RESULTS: In total, 212 healthy volunteers participated. The median (25th - 75th interquartile range) AUC0 - 24h , CLrenal , C3 and C10 , were 10 600 (8470-12 500) ng* hr* mL-1 , 29 (24-34) L* hour-1 , 1460 (1180-1770) and 260 (200-330) ng* mL-1 , respectively, which is in agreement with our previous results. GFRi was correlated with metformin AUC and CLrenal (P < .001). As expected, we found a great pharmacokinetic interindividual variability among the volunteers and no effect of the OCT1 genotype on the AUC0 - 24h . We were unable to reproduce our previous finding of a gene-gene interaction (OCT2 and MATE1) effect on CLrenal in this cohort. CONCLUSION: This study further supports the use of the 2-point LSS algorithm in large pharmacokinetic trials.


Assuntos
Metformina , Área Sob a Curva , Genótipo , Voluntários Saudáveis , Humanos , Hipoglicemiantes , Estudos Prospectivos
5.
Pharmacoepidemiol Drug Saf ; 30(11): 1611-1616, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34435407

RESUMO

PURPOSE: The antihypertensive agent hydrochlorothiazide has recently been linked to increased risk of skin cancer. We sought to describe the impact of the dissemination of these findings on the use of hydrochlorothiazide and health care utilization among antihypertensive users in Denmark. METHODS: In this nationwide observational study, we performed descriptive analyses of a cohort comprising all Danish antihypertensive treatment users January 2016 through September 2020 (n = 1 316 476) with special focus on hydrochlorothiazide users (n = 309 743). Data were retrieved from the Danish nationwide health registries, including the Danish National Prescription Registry. RESULTS: The use of hydrochlorothiazide dropped by 44% from January 2016 to September 2020, with the proportion of all antihypertensive fills constituted by hydrochlorothiazide dropping from 12.7% to 7.2%. This decline was more pronounced among younger patients and patients with a history of skin cancer. Simultaneously, the monthly rate of new hydrochlorothiazide users in Denmark dropped from ≈2350 throughout 2017 to 652 during 2020. The publication of an increased risk of nonmelanoma skin cancer led to an estimated excess of up to 11 510 physical and 22 870 e-mail/phone consultations to general practitioners. No evidence for increased risk of adverse outcomes was found. CONCLUSIONS: The publication of increased risk of skin cancer with hydrochlorothiazide use has led to a marked decline in the use of hydrochlorothiazide in Denmark. A temporary increase in rate of GP contacts was also observed. This highlights the potential impact from disseminating research findings to patients and clinicians.


Assuntos
Hidroclorotiazida , Neoplasias Cutâneas , Estudos de Coortes , Dinamarca/epidemiologia , Humanos , Hidroclorotiazida/efeitos adversos , Sistema de Registros , Risco , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia
6.
Pharmacoepidemiol Drug Saf ; 30(10): 1396-1401, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33960576

RESUMO

BACKGROUND: Hydrochlorothiazide (HCTZ), a common diuretic known to be photosensitizing and previously associated with non-melanoma skin cancer, was recently reported to be associated with two melanoma subtypes, nodular and lentigo, among residents of Denmark. Our goal was to examine whether Danish findings could be replicated in a US cohort, using a similar study design and analysis. METHODS: Among non-Hispanic White enrollees of Kaiser Permanente Northern California, we conducted an analysis of 9176 melanoma cases and 264 781 controls, matched on age, sex and time in health plan. We examined use of HCTZ prior to cancer diagnosis (cases) or comparable date for controls, categorized as never use, ever use and high use (≥50 000 mg). Electronic health records provided data on prescriptions, cancer diagnoses, and covariates. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for education, income and number of dermatology, internal medicine and urgent care visits. RESULTS: We observed a small increase in risk of melanoma, all types combined, associated with high use (≥50 000 mg) of HCTZ (OR = 1.11, 95% CI 1.00-1.23) and no evidence of a dose-response. Risk was more elevated for lentigo subtype (OR = 1.57, 95% CI 1.01-2.42). The somewhat elevated risk for nodular subtype was not statistically significant (OR = 1.22, 95% CI 0.78-1.90). There was very little association of high use with the superficial spreading subtype (OR = 1.05, 95% CI 0.80-1.37). CONCLUSIONS: Our findings support a recent report of an association between high use of HCTZ and increased risk of the lentigo subtype of melanoma.


Assuntos
Hidroclorotiazida , Melanoma , Diuréticos , Escolaridade , Humanos , Hidroclorotiazida/efeitos adversos , Modelos Logísticos , Melanoma/induzido quimicamente , Melanoma/epidemiologia
7.
J Am Acad Dermatol ; 82(2): 326-335, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31150714

RESUMO

BACKGROUND: Several antiepileptic drugs are photosensitizing; however, it is not known whether this confers an increased risk of skin cancer. OBJECTIVE: To examine the association between common antiepileptic drugs and basal cell carcinoma, squamous cell carcinoma (SCC), and malignant melanoma. METHODS: We conducted a nested case-control study identifying skin cancer patients in Denmark from 2004 through 2015 matched 1:10 with disease-free controls. We estimated odds ratios (ORs) for skin cancer associated with high cumulative use of antiepileptic drugs (≥500 defined daily doses) compared with nonuse. RESULTS: Most antiepileptic drugs were not associated with skin cancer. SCC was associated with use of carbamazepine (OR, 1.88; 95% confidence interval, 1.42-2.49) and lamotrigine (OR, 1.57; 95% confidence interval, 1.12-2.22) with evidence of a dose-response relationship for carbamazepine. The estimated absolute risks were low; for example, 6335 person-years of high cumulative exposure to carbamazepine were required for 1 additional SCC to occur. LIMITATIONS: Data on important risk factors for skin cancer, such as sun exposure, were not available. CONCLUSIONS: Most antiepileptic drugs were not associated with skin cancer; however, carbamazepine and lamotrigine were associated with SCC. These findings need to be replicated and characterized further in other settings and have no direct clinical implications.


Assuntos
Anticonvulsivantes/efeitos adversos , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Carbamazepina/efeitos adversos , Carcinoma Basocelular/induzido quimicamente , Carcinoma de Células Escamosas/induzido quimicamente , Estudos de Casos e Controles , Dinamarca/epidemiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Incidência , Lamotrigina/efeitos adversos , Masculino , Melanoma/induzido quimicamente , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamente
8.
Br J Cancer ; 121(11): 973-978, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31673105

RESUMO

BACKGROUND: The antihypertensive agent hydrochlorothiazide has been associated with increased risks of non-melanoma skin cancer (NMSC) and possibly some melanoma subtypes. Previous studies were, however, conducted in predominantly Caucasian populations. We therefore examined the association between hydrochlorothiazide and skin cancer risk in an Asian population. METHODS: By using Taiwan's National Health Insurance Research Database (NHIRD), we conducted three separate case-control studies of lip cancer, non-lip non-melanoma skin cancer and melanoma. Cases (n = 29,082) with a first-ever skin cancer diagnoses (2008-2015) were matched 1:10 to population controls. We estimated odds ratios (ORs) associating hydrochlorothiazide use with skin cancer risk by using conditional logistic regression. RESULTS: Hydrochlorothiazide use showed no overall association with any of the three outcomes: ORs for high cumulative use of HCTZ (≥50,000 mg) were 0.86 (95% CI 0.09-7.81) for lip cancer, 1.16 (95% CI 0.98-1.37) for non-lip NMSC and 1.07 (95% CI 0.65-1.76) for melanoma. There was some evidence of a dose-response pattern for non-lip NMSC, with an OR of 1.66 (95% CI 0.82-3.33) for 100,000-149,999 mg of HCTZ. The null findings were robust across subgroup and sensitivity analyses. CONCLUSION: Use of HCTZ appears safe in terms of skin cancer risk in an Asian population.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hidroclorotiazida/efeitos adversos , Neoplasias Labiais/induzido quimicamente , Neoplasias Labiais/epidemiologia , Melanoma/induzido quimicamente , Melanoma/epidemiologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Risco , Taiwan/epidemiologia
9.
Acta Oncol ; 58(6): 852-858, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30882263

RESUMO

Background: Phthalates are used as excipients in some drug products, and up to a 50-fold increased urinary excretion of phthalate metabolites compared to non-users has been demonstrated in users of such products. In vitro studies have demonstrated that phthalates stimulate mechanisms involved in gastric cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and the risk of gastric adenocarcinomas. Methods: Using the Danish Cancer Registry, we identified all patients with incident gastric adenocarcinoma from 2008 to 2015 (n = 1525). Cancer cases were matched to 10 controls. Linking information retrieved from nationwide Danish registries, we determined individual cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP) and enteric phthalate polymers from prescription drugs. The association between cumulative phthalate exposure and gastric adenocarcinoma was estimated using conditional logistic regression, adjusting for socioeconomical status and drugs or comorbidities known or suspected to modify the risk of gastric adenocarcinoma. Results: No association was seen for the risk of gastric adenocarcinomas among individuals with high cumulative exposure to ortho-phthalates (exceeding 500 mg) (ORadj 1.22, 95% CI: 0.84-1.77). Likewise, no associations were observed individually for DEP (ORadj 1.06 95% CI: 0.63-1.76) or DBP (ORadj 1.32 95% CI: 0.78-2.23). Cumulative exposure to enteric phthalate polymers exceeding 10,000 mg, did not reveal an association with gastric adenocarcinoma (ORadj 0.79, 95% CI: 0.54-1.16) and no association was seen for individual compounds. Additionally, no dose-response pattern was observed across exposure strata (p = .39, test for trend). Conclusion: We did not find an increased risk of gastric adenocarcinoma among Danish users of phthalate-containing drug products. Our study is limited by a low number of cases exposed to high cumulative doses of phthalates.


Assuntos
Contaminação de Medicamentos/estatística & dados numéricos , Excipientes/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Medicamentos sob Prescrição/farmacologia , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/epidemiologia , Idoso , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/tratamento farmacológico
10.
J Am Acad Dermatol ; 80(2): 460-465.e9, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29913261

RESUMO

BACKGROUND: Hydrochlorothiazide use has been associated with markedly increased risk for squamous cell carcinoma. No previous studies have investigated the association between hydrochlorothiazide use and the risk for Merkel cell carcinoma (MCC) and malignant adnexal skin tumors (MAST). OBJECTIVE: To examine the association between hydrochlorothiazide use and the risk for MCC and MAST. METHODS: Using Danish nationwide health registries, we identified all patients with incident MCC or MAST during 2004-2015 and matched the cases individually to cancer-free population controls by risk set sampling. Using conditional logistic regression, we estimated the odds ratios (ORs) and confidence intervals (CIs) associated with cumulative use of hydrochlorothiazide. RESULTS: The adjusted ORs for MCC and MAST associated with high use (≥50,000 mg) of hydrochlorothiazide was 2.3 (95% CI 1.1-4.8) and 3.6 (95% CI 1.9-7.0), respectively, which increased to 3.3 (95% CI 1.3-8.3) and 5.6 (95% CI 2.4-13.3), respectively, with highest use (≥100,000 mg). We found no increased risk for these tumors in analyses of drugs with similar indications as hydrochlorothiazide, except there was a tendency toward an increased risk for MCC associated with the use of furosemide (OR 1.9, 95% CI 0.9-4.0). LIMITATIONS: No data on sun exposure was available. CONCLUSION: Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.


Assuntos
Carcinoma de Célula de Merkel/induzido quimicamente , Hidroclorotiazida/efeitos adversos , Neoplasias de Anexos e de Apêndices Cutâneos/induzido quimicamente , Sistema de Registros , Neoplasias Cutâneas/induzido quimicamente , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/epidemiologia , Carcinoma de Célula de Merkel/patologia , Estudos de Casos e Controles , Dinamarca , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias de Anexos e de Apêndices Cutâneos/epidemiologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Razão de Chances , Prognóstico , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Análise de Sobrevida
11.
Epidemiology ; 29(3): 442-447, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29337844

RESUMO

BACKGROUND: The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. METHODS: We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. CONCLUSIONS: The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.


Assuntos
Bases de Dados Factuais/normas , Melanoma/epidemiologia , Sistema de Registros/normas , Idoso , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/fisiopatologia
12.
J Am Acad Dermatol ; 78(4): 673-681.e9, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29217346

RESUMO

BACKGROUND: Hydrochlorothiazide, one of the most frequently used diuretic and antihypertensive drugs in the United States and Western Europe, is photosensitizing and has previously been linked to lip cancer. OBJECTIVE: To examine the association between hydrochlorothiazide use and the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: From the Danish Cancer Registry, we identified patients (cases) with nonmelanoma skin cancer (NMSC) during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative hydrochlorothiazide use (in 1995-2012) was assessed from the Danish Prescription Registry. Using conditional logistic regression, we calculated odds ratios (ORs) for BCC and SCC associated with hydrochlorothiazide use. RESULTS: High use of hydrochlorothiazide (≥50,000 mg) was associated with ORs of 1.29 (95% confidence interval [CI], 1.23-1.35) for BCC and 3.98 (95% CI, 3.68-4.31) for SCC. We found clear dose-response relationships between hydrochlorothiazide use and both BCC and SCC; the highest cumulative dose category (≥200,000 mg of HCTZ) had ORs of 1.54 (95% CI, 1.38-1.71) and 7.38 (95% CI, 6.32-8.60) for BCC and SCC, respectively. Use of other diuretics and antihypertensives was not associated with NMSC. LIMITATIONS: No data on sun exposure were available. CONCLUSIONS: Hydrochlorothiazide use is associated with a substantially increased risk of NMSC, especially SCC.


Assuntos
Anti-Hipertensivos/efeitos adversos , Carcinoma Basocelular/induzido quimicamente , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/epidemiologia , Hidroclorotiazida/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco
17.
Eur J Cancer ; 202: 114023, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518533

RESUMO

BACKGROUND: Clinical trials have demonstrated promising outcomes for adjuvant immunotherapy in patients with resected melanoma. Real-life data provide valuable insights to support patient guidance and treatment decisions. METHODS: Observational population-based study examining a national cohort of patients with resected stage III-IV melanoma referred for adjuvant therapy. Data were extracted from the Danish Metastatic Melanoma Database (DAMMED). RESULTS: Between November 2018 and January 2022, 785 patients received adjuvant anti-PD-1. The majority had stage III resected melanoma (87%), normal LDH levels (80%), and performance score 0 (87%). Patients were followed for a median of 25.6 months (95%CI 24-28). The median recurrence-free survival (RFS) and melanoma-specific survival (MSS) were not reached. The RFS was 78% (95%CI 75-81), 66% (63-70), and 59% (55-63); MSS was 97% (95-98), 93% (91-95), and 87% (84-90) at 1-, 2-, and 3-year; respectively. Less than half (42%) of the patients finalized planned therapy, 32% discontinued due to toxicity, and 19% due to melanoma recurrence. Patients discontinuing adjuvant treatment prematurely, without recurrence, had similar outcomes as patients finalizing therapy. In a multivariable analysis, ipilimumab plus nivolumab did not improve outcomes compared to ipilimumab monotherapy as a first-line metastatic treatment after adjuvant anti-PD-1. CONCLUSION: Survival outcomes in real-world patients with melanoma treated with adjuvant anti-PD-1 align with results from the randomized controlled trials. Patients discontinuing therapy prematurely, for other reasons than recurrence, had similar outcomes as patients finalizing planned treatment. First-line metastatic treatment with ipilimumab and nivolumab post-adjuvant anti-PD-1 did not show improved outcomes compared to ipilimumab/anti-PD-1 monotherapy.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Ipilimumab/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/induzido quimicamente , Adjuvantes Imunológicos/uso terapêutico , Imunoterapia/métodos
18.
Basic Clin Pharmacol Toxicol ; 133(2): 124-129, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37309284

RESUMO

BACKGROUND: Serotonin syndrome is a potentially life-threatening syndrome with manifestations spanning from mild adverse effects to life-threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation. OBJECTIVES: This review aims to provide a clinically focused overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis and treatment, as well as classifying serotonergic drugs and their mechanism of action. The pharmacological context is emphasized, as it is crucial for the detection and management of serotonin syndrome. METHODS: Focused review based on a literature search using the PubMed database. FINDINGS AND CONCLUSION: Serotonin syndrome can occur through therapeutic use or overdose of a single serotonergic drug or as a drug interaction between two or more serotonergic drugs. Central clinical features consist of neuromuscular excitation, autonomic dysfunction and altered mental status, occurring in a patient undergoing new or altered serotonergic therapy. Early clinical recognition and treatment are crucial to prevent significant morbidity.


Assuntos
Transtornos Mentais , Síndrome da Serotonina , Humanos , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/diagnóstico , Síndrome da Serotonina/terapia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Serotoninérgicos/efeitos adversos
19.
Eur J Cancer ; 195: 113392, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37924648

RESUMO

BACKGROUND: The introduction of modern therapies improved the median survival of patients with metastatic melanoma (MM). Here, we determined the real-world impact of modern treatments on the long-term survival of MM. METHODS: In a population-based study, we extracted all cases of MM diagnosed in four non-consecutive years marked by major changes in available 1st line treatments (2012, 2014, 2016, and 2018) from the Danish MM Database. Patients were grouped into "trial-like" and "trial-excluded" based on common trial eligibility criteria. RESULTS: We observed a sustained improved survival of "trial-like" patients diagnosed in 2016 or in 2018, compared to 2012 or 2014, but no major differences in 2018 versus 2016. In contrast, while survival of "trial-excluded" patients in 2016 was better compared to 2014 and 2012, survival in 2018 was improved over all previous years. We then developed a prognostic model based on multivariable stratified Cox regression, to predict the survival of newly diagnosed MM patients. Internal validation showed excellent discrimination and calibration, with a time-area-under-the-curve above 0.79 at multiple time horizons, for up to four years after diagnosis. CONCLUSIONS: The introduction of modern treatments such as anti-PD-1 has led to a sustained, improved survival of real-world patients with MM, regardless of their eligibility for clinical trials. We provide an updateable prognostic model that can be used to improve patient information. Overall, these data highlight a positive population-based impact of modern treatments and can help health technology assessment agencies worldwide to evaluate the appropriateness of drug pricing based on known cost-benefit data.


Assuntos
Melanoma , Humanos , Melanoma/secundário , Prognóstico
20.
Melanoma Res ; 32(3): 173-182, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35256571

RESUMO

Novel medical therapies have revolutionized outcome for patients with melanoma. However, patients with melanoma brain metastases (MBM) still have poor survival. Data are limited as these patients are generally excluded from clinical trials, wherefore real-world data on clinical outcome may support evidence-based treatment choices for patients with MBM. Patients diagnosed with MBM between 2008 and 2020 were included retrospectively. Patient characteristics, treatment, and outcome data were recorded from The Danish Metastatic Melanoma Database, pathology registries, electronic patient files, and radiation plans. Anti-programmed cell death protein 1 antibodies and the combination of BRAF/MEK-inhibitors were introduced in Denmark in 2015, and the cohort was split accordingly for comparison. A total of 527 patients were identified; 148 underwent surgical excision of MBM, 167 had stereotactic radiosurgery (SRS), 270 received whole-brain radiation therapy (WBRT), and 343 received systemic therapies. Median overall survival (mOS) for patients diagnosed with MBM before and after 2015 was 4.4 and 7.6 months, respectively. Patients receiving surgical excision as first choice of treatment had the best mOS of 10.9 months, whereas patients receiving WBRT had the worst outcome (mOS, 3.4 months). Postoperative SRS did not improve survival or local control after surgical excision of brain metastases. Of the 40 patients alive >3 years after diagnosis of MBM, 80% received immunotherapy at some point after diagnosis. Patients with meningeal carcinosis did not benefit from treatment with CPI. Outcome for patients with MBM has significantly improved after 2015, but long-term survivors are rare. Most patients alive >3 years after diagnosis of MBM received immunotherapy.


Assuntos
Neoplasias Encefálicas , Melanoma , Radiocirurgia , Neoplasias Cutâneas , Neoplasias Encefálicas/secundário , Irradiação Craniana , Humanos , Melanoma/patologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA